Stop mutations are also reported in inhibitor cases, whereas missense mutations carry the lowest inhibitor risk [45, 49]. The clinical manifestations of haemophilia A and B are similar; however, differences in bleeding frequency, clinical scores, prophylaxis use and requirement for joint prosthesis have been highlighted and conflicting evidence continues to be debated [28, 42, 50, 51]. Already in 1959, the first report about a milder clinical expression of haemophilia B in comparison with haemophilia A was provided by Armand Quick [52]. More recently, an interesting observation was carried out during the validation of a scoring system aimed at assessing the clinical severity

of this website haemophilia in patients without inhibitors [28]. This composite HSS included: incidence of joint bleeding; orthopaedic joint score and factor consumption. The HSS result

was higher in severe haemophilia A than in severe haemophilia B [28]. However, in contrast with these results, a subsequent study carried out in a single centre in Italy did not confirm any significant difference between patients with haemophilia A and B [53]. In a Canadian survey conducted in 2006 to collect information on the use of regular prophylaxis, it was www.selleckchem.com/products/icg-001.html shown that this therapeutic regimen was less frequently adopted by patients with severe haemophilia B than by those with severe haemophilia A (32% vs. 69%) [50]. Even more unexpectedly, it appeared that among patients with haemophilia B a limited proportion of children younger than 2 years of age was on prophylaxis (20%), while more than half of the patients with haemophilia A belonging to the same-age Leukotriene-A4 hydrolase group were already on regular prophylaxis

[50]. A different retrospective survey was carried out by Italian investigators to compare the orthopaedic outcome in severe haemophilia A and B. All joint arthroplasties performed at the 29 participating centres were analysed [42]. Overall, 347 surgeries were performed in 268 patients (328 operations in 253 patients with severe haemophilia A, 19 in 15 with severe haemophilia B). Patients with haemophilia A showed a three-fold greater risk of undergoing joint replacement and this result was confirmed after adjustment for confounders (age and viral infections) [42]. Since joint replacement is an indirect marker of advanced arthropathy and the most solid long-term outcome of the severe bleeding phenotype in haemophilia, this piece of evidence supports the view that haemophilia B has a milder bleeding tendency than haemophilia A [42]. Nevertheless, a single-centre study carried out in the Netherlands did not confirm any difference in the arthroplasty rate across haemophilia types [54]. Other conflicting results came from a small study conducted in Canadian patients with severe and moderate haemophilia [51].